Highly Enantioselective Preparation of Multifunctionalized Propargylic Building Blocks

Halogenated propargylic alcohol 2 a (X = Cl, R = Ph) was prepared by the enzymatic reduction of the corresponding ketone 1 a with excellent enantioselectivity and chemical yield. Both enantiomers were synthesized with high total turnover numbers of the catalysts and cofactors. Other halogenated alkynones 1 were also suitable substrates for the enzymes. Alcohols 2 were converted into propargylic epoxides 3 under mild conditions to give multifunctionalized building blocks. X = Cl, Br; R = H, Ph, trimethylsilyl, tert-butyldimethylsilyl; ADH = alcohol dehydrogenase; DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene.